Dr DuBois has discovered that the concentration of nitric oxide gas in air withdrawn slowly from the nose in man is one thousand times more concentrated (12 parts per million) than a comparable sample of expired air from human lungs (12 parts per billion). The overall aim of this proposal is to find out where the nitric oxide arises in the nasal cavity, what tissues generate it, how it varies with abnormality, and whether it serves a useful purpose in maintaining health or combating disease of the nasal cavity. To accomplish the broad aims of this proposal, Dr. DuBois first measured the rate of production and removal of nitric oxide in the nasal cavity of man, then began a survey of nitric oxide concentrations in noses of rats, guinea pigs, cats, dogs, pigs, and monkeys. He now has to collect cells and tissues from the nasal cavity in order to stain these for specific enzymes that take part in nitric oxide synthesis. Having stained and located enzymes, such as iNOS and cNOS, in epithelial cells, endothelial cells, or neural tissue the team will compare the rate of nitric oxide production and/or destruction in vitro with the rates measured in vivo, taking into account the dimensions of the nose and its tissues in animals and man. The functional role of nitric oxide in the nasal cavity will be deduced not only from the location of its synthesis, and type of tissue concerned, but also from pharmacological and biochemical stimulation or suppression of nitric oxide synthesis and enhancement or suppression of host- defense mechanisms including immunologic, allergic, cellular, and vascular. Because nasal passages are the entrance point for inhaled particles, microbial agents, allergens, irritants, odors, and toxic gases into the respiratory tract, the response of the membranes in the nose to those substances can indicate what is inhaled and how the body reacts to it. The applicants speculate that nitric oxide, a ubiquitous mediator, may mediate some of the host responses, and, by suppressing bacterial growth, may help resist microbial invasion. Their studies are designed to find out the answers to the above questions.